Non Small Cell Lung Cancer
Conditions
Brief summary
A study evaluating the effects of food intake on the pharmacokinetic (PK) profiles of TGRX-326 and the effect of different drug specifications on human bioavailability for TGRX-326, a drug indicated for non-small cell lung cancer treatment
Detailed description
This study is designed as single-center, randomized, open-label, 3-cycle, 6-sequence and crossover design to evaluate 1) food effect on PK profile of TGRX-326; 2) effect of different specifications of TGRX-326 on human bioavailability. Safety for food effect on TGRX-326 and safety for different TGRX-326 specifications were also evaluated.
Interventions
DRUGcycle 1: treatment drug
for cycle 1 treatment: participants are given the oral treatment specification (60 mg \*1 pill)
DRUGcycle 1: reference drug
for cycle 1 treatment: participants are given the oral reference specification (5 mg \*2 pills + 25 mg \* 2 pills)
BEHAVIORALcycle 1: fasted
for cycle 1 treatment: participants are asked to take the drug fasted
BEHAVIORALcycle 1: food
for cycle 1 treatment: participants are asked to take the drug after food intake
DRUGcycle 2: treatment drug
for cycle 2 treatment: participants are given the oral treatment specification (60 mg \*1 pill)
DRUGcycle 2: reference drug
for cycle 2 treatment: participants are given the oral reference specification (5 mg \*2 pills + 25 mg \* 2 pills)
BEHAVIORALcycle 2: fasted
for cycle 2 treatment: participants are asked to take the drug fasted
BEHAVIORALcycle 2: food
for cycle 2 treatment: participants are asked to take the drug after food intake
DRUGcycle 3: treatment drug
for cycle 3 treatment: participants are given the oral treatment specification (60 mg \*1 pill)
DRUGcycle 3: reference drug
for cycle 3 treatment: participants are given the oral reference specification (5 mg \*2 pills + 25 mg \* 2 pills)
BEHAVIORALcycle 3: fasted
for cycle 3 treatment: participants are asked to take the drug fasted
BEHAVIORALcycle 3: food
for cycle 3 treatment: participants are asked to take the drug after food intake
Sponsors
The First Affiliated Hospital of Bengbu Medical University
Shenzhen TargetRx, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
This is a PK assessment study, hence only bio-sample analysis personnel were masked for the type of treatment received for each sample to avoid bias in analysis. Other study personnel, including participants, investigators and staffs were not masked for treatment types.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* able to understand the purpose, methods and possible adverse events of the study and agree to volunteering consent before the start of study * healthy subject; male or female * Age between 18 and 55 (inclusive) * body mass index (BMI) between 19.0 and 26.0 (inclusive), male weight \<=50 kg, female weight \<=45 kg * normal/ clinically insignificant test results (including physical exam, laboratory tests, 12-lead ECG, chest x-ray, etc.) * participant/partner of the participant does not have plans for child bearing from screening until 6 months after study, and is willing to take contraceptive measures during study period and for 6 months, and does not have plans to donate sperm/egg during the said period
Exclusion criteria
* history of allergic reactions, or allergic to any components to the study drugs that by investigator's judgement unsuitable for the study * any clinically significant conditions that could affect study outcomes, safety or compliance * history of major surgery within 3 months before first dose, or have plans to receive surgery during the study, or history of any surgery that could affect drug absorption, distribution, metabolism and excretion * have difficulties to receive venous needle puncture, or cannot tolerate venous needle puncture, or history of hematophobia or needle sickness * history of substance abuse * have special food requirement or cannot follow food requirement of the study, or lactose intolerant * use of any investigational drug or participation of any clinical study (for drug or medical device) within 3 months before first dose, or cannot participate the study in person/on site * history of blood donation, blood loss (\>= 400 mL, excluding normal blood loss during female menstrual period), or reception of blood transfusion within 3 months before screening * history of daily cigarette consumption of more than 5 within 3 months before screening, or cannot avoid using cigarette/tabacco products during the study * history of alcohol abuse (more than 14 units of alcohol per week) within 3 months before screening, or cannot avoid alcohol consumption during study * history of large tea/coffee/caffeinated drink intake (more than 8 cups per day) within 3 months before first dose * history of irregular dietary schedule within 1 months of first dose (including, dieting, overeating, low sodium intake, etc.) * use of any prescription / over-the-counter drug, or Chinese herbal medication, or health supplementary products within 14 days of test article administration * vaccination within 14 days before first test article administration, or have plans to receive vaccination during the study period * any one positive result for hepatitis-B surface antigen, Hepatitis C antibody, HIV antibody or syphilis antibody * alcohol breathing test results of \> 0.0 mg/100mL for blood alcohol concentration * positive test results on substance use (including, morphine, methylamphetamine, ketamine, tetrahydrocannabinol, methylene-dioxy-methyl-amphetamine) * female in pregnancy or breastfeeding period, or positive pregnancy test result * history of unprotected sexual activities within 14 days before first dose * consumption of food or drink rich in caffeine/xanthine (such as chocolate, coffee, tea, coke) or food/food product of grapefruit, dragon fruit, mango, tangerine, or any food that could affect drug absorption, distribution, metabolism and excretion * any reasons that is deemed unsuitable for study participation as determined by investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Cmax | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | Maximum concentration of TGRX-326 measured in plasma |
| Plasma AUC(0-t) | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | Area Under drug concentration-time curve (AUC) from time 0 to last measureable timepoint for TGRX-326 as measured in plasma |
| Plasma AUC(0-inf) | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | Area Under drug concentration-time curve from time 0 to infinity for TGRX-326 as measured in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Elimination half-life (T1/2-Z) | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | Time for TGRX-326 to decrease from maximum plasma concentration to half of maximum plasma concentration |
| AUC(%Extrap) | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | Calculated percentage of Area under curve for AUC(0-inf) that is from last measurable timepoint ot infinity, calculated based on TGRX-326 plasma concentration over time curve. |
| Adverse events/serious adverse events | through completion of the study, a total duration of 37 days | to record and analyse subjects with adverse events (AEs) and serious adverse events (SAEs) |
| Plasma clearance (CL/F) | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | Apparent clearance of TGRX-326 in plasma |
| Plasma volume of distribution (Vz/F) | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | Apparent volume of distribution of TGRX-326 in plasma |
| Plasma Tmax | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | Time to maximum concentration of TGRX-326 measured in plasma |
| terminal elimination rate constant (lambda-z) | During treatment period on Day 1 of each of three cycles (each cycle is one day, and there is a 10-day washout period between two cycles) | terminal elimination rate constant calculated from plasma TGRX-326 concentrations |
Countries
China
Outcome results
None listed